An investigation into certain aspects of the biology of hormone- dependent mammary tumors is proposed. These unusual neoplasms found in certain strains of inbred mice arise during pregnancy, grow very rapidly until paturition, and thereafter regress, usually disappearing within a week following birth. Tumors arise at the same site in subsequent pregnancies. The nature of this extreme hormone dependency will be studied by establishing serially transplanted tissue lines which, when propagated in non-pregnant hosts is morphologically normal, but which rapidly converts to a tumorous growth phase during pregnancy. These transplant lines will provide a source of tissue for in vitro studies in which entire, previously transplanted mammary glands will be placed in organ culture, and their response to various hormonal regimes will be evaluated. In this manner the endocrine requirements for maintenance of hormone-dependent tumor growth will be determined, as will be the hormones necessary for the transition from normal to tumorous growth phases. In addition, the cellular events associated with tumor development will be studied, with emphasis upon patterns of cell proliferation. The availability of hormone-dependent tumor tissues, which in several respects resembles human mammary tumors, provides a unique opportunity for the study of endocrine interactions in neoplasia, and should provide an important model for the investigation of basic mechanisms of tumorigenesis, with clear relevance to human breast cancer.